Abstract

Botanical preparations are widely used by patient with cancer in Korea, Japan and China. Rhus verniciflua Stokes (RVS) has traditionally been used as a medicinal ingredient for the therapy of stomach and uterine cancer. In this study, we showed that exposure to an ethanol extract of RVS (50 μg/ml) resulted in a synergistic inhibitory effect on cell growth in AGS cells. Growth inhibition was related with the inhibition of proliferation and induction of apoptosis. The extract induces G₁-cell cycle arrest through the regulation of cyclins, the induction of p27^Kip1, and decrease the CDK2 kinase activity. The upregulated p27^Kip1 level is caused by protein stability increment by the reduction of Skp2, a key molecule related with p27^Kip1 ubiquitination and degradation, and de novo protein synthesis. RVS extract induces apoptosis through the expression of Bax, poly(ADP-ribose) polymerase (PARP) and activation of caspase-3. RVS extract induces G₁-cell cycle arrest via accumulation of p27^Kip1 controlled by Skp2 reduction and apoptosis passing through an intrinsic pathway in human gastric cancer cells but not in normal cells, therefore we suggest that this extract could be a candidate medicine or compound for the development of novel class of anti-cancer drugs.

Author keywords

Apoptosis; Cell cycle; p27^Kip1; Rhus verniciflua Stokes; Skp2

Indexed keywords

EMTREE drug terms: alcohol; CASP3 protein, human; caspase; caspase 3; cell cycle protein; cyclin dependent kinase inhibitor 1A; cyclin dependent kinase inhibitor 1B; messenger RNA; plant extract

EMTREE medical terms: apoptosis; article; cell cycle; cell division; cell line; cell survival; chemistry; dose response; drug effect; genetics; human; isolation and purification; metabolism; Northern blotting; pathology; physiology; poison ivy; stomach tumor; tumor cell line; upregulation

MeSH: Apoptosis; Blotting, Northern; Caspase 3; Caspases; Cell Cycle; Cell Cycle Proteins; Cell Division; Cell Line; Cell Line, Tumor; Cell Survival; Cyclin-Dependent Kinase Inhibitor p21; Cyclin-Dependent Kinase Inhibitor p27; Dose-Response Relationship, Drug; Ethanol; Humans; Plant Extracts; Rhus; RNA, Messenger; Stomach Neoplasms; Up-Regulation
Medline is the source for the MeSH terms of this document.

Chemicals and CAS Registry Numbers: alcohol, 64-17-5; caspase 3, 169592-56-7; caspase, 186322-81-6;CASP3 protein, human, EC 3.4.22.-; Caspase 3, EC 3.4.22.-; Caspases, EC 3.4.22.-; Cell Cycle Proteins; Cyclin-Dependent Kinase Inhibitor p21; Cyclin-Dependent Kinase Inhibitor p27, 147604-94-2; Ethanol, 64-17-5; Plant Extracts; RNA, Messenger